In infarction diseases such as myocardial infarction, cerebral infarction, and mesenteric thrombosis, ischemia reperfusion therapy which allows blood to reflow in tissue which was in an ischemic state by interruption of blood flow is often carried out by mechanically expanding the vessel in the infraction area or dissolving thrombi. In a transplanted organ after organ transplantation, blood flow is similarly restarted in tissue to which blood circulation ceased. It is known that when blood flow is restarted in a tissue, oxygen is suddenly delivered to the tissue which has been in an ischemic state, resulting in the occurrence of various physiological reactions including the generation of active oxygen (oxygen radicals) or other free radicals, neutrophilic infiltration, and activation of platelets, which cause worsening of organ derangement such as damage to the cardiac muscle (for example, myocardial infarction). Such phenomenon is referred to as ischemia-reperfusion injury or simply as reperfusion injury.
Nitrogen monoxide (NO) is a vasodilative substance derived from the endothelium. It is known that administration of nitrogen monoxide gas by inhalation has effects such as lowering the pulmonary arterial pressure by vasodilation in the lungs, increasing oxygenation of the entire body, suppressing activation of platelets, and suppressing activation and adhesion/coagulation of leukocytes. With respect to ischemia-reperfusion injury, inhalation of nitrogen monoxide gives a certain effect as demonstrated by the fact that it decreases the infarcted area and is effective at alleviating myocardial injury (see below-listed Patent Document 1 and Non-Patent Document 1).
However, while nitrogen monoxide has such protective activities, it has the problem that it reacts particularly with superoxide anions, which are produced intracellularly or extracellularly, resulting in the production of peroxynitrite which has an extremely high toxicity to the tissues. Accordingly, there is a high risk of side effects caused by the inhalation of nitrogen monoxide.
In recent years, it has been demonstrated that hydrogen (H2), which is a reducing agent, selectively reacts with highly reactive species of active oxygen (such as hydroxyl radical <.OH> and peroxynitrite <ONOO−>) and eliminates them. It is known that if hydrogen gas is administered by inhalation through the lungs, hydrogen is delivered to the entire body through the blood and can suppress lesions associated with oxygen radicals and eliminate free radicals which have a strong oxidizing power to cause cell injury. It has been reported that in ischemia reperfusion models of cerebral infarction and ischemia reperfusion models of the liver in mice, damage to organs and tissue at the time of ischemia reperfusion can be decreased by hydrogen (see below-listed Non-patent Documents 2 and 3). However, it is difficult to suppress neutrophilic infiltration and platelet activation which are observed at the time of ischemia reperfusion using only hydrogen inhalation.